A high-quality human reference panel reveals the complexity and distribution of genomic structural variants

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation. Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elem... Mehr ...

Verfasser: Hehir-Kwa, Jayne Y
Marschall, Tobias
Kloosterman, Wigard P
Francioli, Laurent C
Baaijens, Jasmijn A
Dijkstra, Louis J
Abdellaoui, Abdel
Koval, Vyacheslav
Thung, Djie Tjwan
Wardenaar, René
Renkens, Ivo
Coe, Bradley P
Deelen, Patrick
de Ligt, Joep
Lameijer, Eric-Wubbo
van Dijk, Freerk
Hormozdiari, Fereydoun
Uitterlinden, André G
van Duijn, Cornelia M
Eichler, Evan E
de Bakker, Paul IW
Swertz, Morris A
Wijmenga, Cisca
van Ommen, Gert-Jan B
Slagboom, P Eline
Boomsma, Dorret I
Schönhuth, Alexander
Ye, Kai
Guryev, Victor
Dokumenttyp: Artikel
Erscheinungsdatum: 2016
Reihe/Periodikum: Nature Communications, vol 7, iss 1
Verlag/Hrsg.: eScholarship
University of California
Schlagwörter: Biological Sciences / Bioinformatics and Computational Biology / Genetics / Epidemiology / Health Sciences / Human Genome / Biotechnology / 2.1 Biological and endogenous factors / Aetiology / Generic health relevance / Algorithms / Chromosomes / Computational Biology / Gene Deletion / Genome / Human / Genomic Structural Variation / Genomics / Genotype / Haplotypes / Humans / INDEL Mutation / Linkage Disequilibrium / Netherlands / Polymerase Chain Reaction / Polymorphism / Single Nucleotide / RNA / Sequence Analysis / DNA / Software / Genome of the Netherlands Consortium
Sprache: unknown
Permalink: https://search.fid-benelux.de/Record/base-27570921
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://escholarship.org/uc/item/54n4z1k5

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation. Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion are previously under reported variants sized between 21 and 100 bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with SVs and demonstrate that our panel facilitates accurate imputation of SVs in unrelated individuals.